Sunday, May 5, 2013

Can Anti-HIV Drugs Stop MS?

Animation of the structure of a section of DNA. The bases lie horizontally between the two spiraling strands. (Photo credit: Wikipedia)

(Readers who receive these posts via email are advised that this essay contains a video, which cannot be viewed in the email version. Please go to the Wheelchair Kamikaze website (click here) to view the video…)

I imagine the above headline might have furrowed a few eyebrows and crinkled some foreheads when first viewed by readers. HIV (the virus that causes AIDS) has nothing to do with MS, does it? Has Marc finally lost his last marble? Don’t MS patients have enough to worry about without having to contemplate AIDS?

Yes, MS patients certainly do have enough to worry about, and no, the virus that causes AIDS has nothing to do with multiple sclerosis. HIV, though, is a retrovirus, and, strange as it might sound, there is increasing evidence that ancient retroviruses that have become incorporated into the human genome through millions of years of evolution may play a key role in the MS disease process. This might seem like something out of a science fiction novel, but this discovery of prehistoric viral material in human DNA has the potential to completely change the way we understand and treat MS and other diseases (including cancer), and could potentially lead to – dare I say it – a cure.

There are currently two clinical trials underway attempting to shut down these ancient retroviruses in MS patients, and one of them uses a currently available anti-HIV drug. More on these trials a bit later, but first a little background, starting with a quick overview of virology. I know the mere prospect of “a quick overview of virology” is apt to make eyes glaze over throughout the Internet, but please bear with me, I’ll try to keep it as painless as possible.

We’re all familiar with viruses, the little buggers that cause influenza, the common cold, and a many other diseases. Of course, bacteria also cause diseases, but viruses and bacteria, though both infectious agents, are very different beasties. Bacteria are living organisms, and when someone suffers a bacterial infection they can usually be treated with antibiotics, drugs which kill the guilty bacteria and thereby cure the patient. Antibiotics have no effect on viruses, though, because viruses aren’t alive, and therefore can’t be killed. Viruses are kind of like the zombies of the pathogen world, undead infectious agents that exist only to infect living things. The fact that viruses are “undead” is what makes viral diseases so hard to treat, and why we still don’t have a cure for the common cold.

Unlike living bacteria, which can reproduce all on their own, undead viruses replicate by hijacking their victims’ cells and then using the resources within those cells to reproduce themselves. Most viruses kill the cells they invade by replicating to the point where the infected cells burst, releasing the reproduced viruses and thus spreading viral infection throughout the body. Another type of virus, though, called a retrovirus, actually inserts itself into the host cell’s DNA, and in effect become part of the organism they have infected, commandeering the host’s genetic material and cellular mechanisms to replicate themselves without destroying the cells they have invaded. This makes retroviral diseases (such as AIDS) extremely hard to treat, and coming up with ways to neutralize retroviruses has presented medical science with one of its most daunting challenges.

Now, here comes the really strange part. When the Human Genome Project (click here) completed the incredibly complex task of mapping all of the genes contained in human DNA, it was discovered that 8% of our genetic material is comprised of the remnants of ancient retroviruses, many of which inserted themselves into our genetic material tens of millions of years ago during the evolutionary process, before humans were even human. These retroviruses were at one time in the distant past infectious, but have long since been rendered dormant, and it was initially thought that they were nothing more than “junk DNA”, left over genetic material that plays no role whatsoever in the development or functioning of a human being. These ancient retroviruses that are now part of the human genome were named Human Endogenous Retroviruses, or HERVs. They are a part of all of us, genetic remnants of our evolutionary history.

Recent research into HERVs has provided tantalizing clues that rather than always remaining dormant, in certain circumstances these ancient viruses can be activated and may play a key role in many diseases, including multiple sclerosis, many autoimmune diseases, some cancers, and even schizophrenia (click here, here, here and here). The mechanism by which HERVs are activated are not fully understood, but the prevailing thought is that the presence of other viruses and environmental agents, such as Epstein-Barr virus (click here), the human herpesviruses (click here), and other environmental triggers, or a combination of these elements, may “wake” these bits of ancient viruses that are part of our DNA. Once activated, this ancient retroviral DNA can cause our own cells to secrete proteins and antigens that may identify the host cell as a hostile invader, or otherwise initiate critical disease processes.

Within the last five years or so, it’s been established that virtually every MS patient is infected with Epstein-Barr virus (click here), which is best known for causing mononucleosis/glandular fever. I know, many of you are saying, “but I never had mononucleosis or glandular fever, so I don’t have EBV!” The fact is that in the majority of cases infection with Epstein-Barr virus does not result in Mono, but rather can present as a bad cold or flu, or can even be completely asymptomatic. Over 90% of the general population is infected with EBV, but, remarkably, it appears that 100% of MS patients carry the bug. MS researchers have long puzzled over the role EBV might play in the MS disease process, since EBV infection alone certainly can’t be the sole cause of MS, otherwise far more people would have multiple sclerosis. The link between EBV and HERVs could finally clear up this mystery, for if a long-term EBV infection can turn on ancient retroviruses embedded in the DNA of genetically susceptible people, the connection between EBV and MS might finally be understood (click here).

Though the connection between HERVs and MS has yet to be proven, more and more evidence appears to be pointing in that direction (click here), and the hypothesis does pull together some of the “wildcard” factors that have confounded MS researchers for decades. Among these factors are indicators that there is an infectious component to MS, such as the existence of “MS clusters”, geographic locations where MS appears to run rampant among the local population (click here), and migratory studies which show that migration from areas of high MS to areas of low MS before the age of 15 decreases the risk of getting multiple sclerosis, with the reverse being true as well (click here). Through the years many possible infectious candidates have been proposed, to no avail, but if the HERVs theory is correct, it’s a combination of infectious agents, including some hiding in a patient’s own DNA, that may be responsible.

Both EBV (which is itself a human herpesvirus) and retroviruses have proven to be extremely difficult to eradicate, as can be illustrated by the fight against HIV. HIV is a retrovirus, and although medical science has made great strides in developing drugs that keep HIV infection under control (deaths from AIDS have plummeted in the last decade), there is still no way to completely eradicate the virus from the body of an infected person. One anti-HIV drug, Raltegravir (brand name Isentress) (click here) has proven to be quite effective in combating HIV, though, and also shows promise as an anti-EBV weapon.

A clinical trial now underway at Queen Mary University in London, England, called be INSPIRE trial (click here), is attempting to use Raltegravir to treat MS patients. Researchers hope that the drug will deactivate any activated retroviral material in the DNA of MS patients, while perhaps also combating EBV, and thus stop multiple sclerosis in its tracks. Another group of researchers in Switzerland are trying to accomplish the same outcome using an experimental drug that targets a protein on a specific HERV that is thought to be directly connected with MS, which has been dubbed the Multiple Sclerosis Associated Retrovirus, or MSRV (click here). This is a small, 10 person Phase 2 trial whose primary goal is to establish the safety of the experimental drug being tested. Results from the INSPIRE trial, which is just getting underway, are not expected until August, 2014, and the results from the Swiss trial are expected in July of this year.

It’s impossible to overstate the potential that this research has to completely reshape the multiple sclerosis landscape, with vast implications impacting the quest to wipe out many other horrendous diseases as well. If indeed prehistoric viruses embedded within our own DNA are at work driving the MS disease process, shutting down these viruses could amount to a cure. Yes, a cure for multiple sclerosis! Though it may be hard to believe, there is precious little work being done elsewhere to uncover the roots of MS, as so much research time and money is devoted towards finding newer and more effective (and more profitable) ways to suppress the aberrant immune response that is seen in the disease, a response that is in fact a symptom of some as yet unknown underlying cause. All of the current crop of MS drugs, and the vast majority of those in the experimental pipeline, either modulate or suppress the immune system, a mechanism of action which can sometimes dramatically improve the quality of life of RRMS patients, but will never do anything to cure multiple sclerosis. The research going on in London and Switzerland at last holds out hope for a cure, and represent a radical rethinking of the cause of many of the diseases that plague mankind.

My intuition and instincts tell me that these research scientists are onto something, and it’s something potentially huge. It’s long been known that genetics play a role in MS, and it has also long been suspected that infectious agents are at work. The idea that Human Endogenous Retroviruses, bits of viruses that are in a very real way a part of us, encoded into our DNA, could play a key role in the MS disease process ties together both of these observations, as well as several others. The evidence to support this idea is mounting, and to me this hypothesis feels right in a way that no other MS related theory I’ve come across has before. Of course, you can (and probably should) take my “gut feelings” with a grain of salt, but I find myself brimming with enthusiasm that the science of treating MS is finally moving in the right direction. Of course, as I’ve often cautioned before, it’s vital not to let hope eclipse reason, and this research might well lead to nothing. But, somehow, I just don’t think that it will…

Here’s a terrific video presentation by one of the lead researchers involved in the INSPIRE trial, which does a great job of explaining the research and the ideas behind it in a very accessible, easy to understand manner. I urge all readers to watch this video, as the information it contains has tremendous potential…

23 comments:

Gosh, very interesting Marc. I have tested positive for Epstein Barr (having had mono as a teen), and I have had shingles 5 times (three times before any MS symptoms). I'll be keeping my eye on this research! Thanks for the info.

This does sound promising, Marc, and thank you for bringing to our attention. If it does work, and God I hope it does, I wonder what shenanigans will emerge to prevent the drug from coming to a pharmacy near you. What, me cynical? Nah.

Very interesting stuff, Marc...thank you for your clear explanation and continuing research. My family is chock full of supposed autoimmune diseases so this will interest everyone. And now I understand what a retrovirus is!

So often science gets railroaded in the logic of A means B which after some study means C... This logic progression is certainly progress in terms of accumulating knowledge. Sadly with MS and other diseases of late, somewhere around the theoretical M, it is determine M brings $, a one $ brings a quest for $2. Suddenly what seemed a relentless march towards the endpoint of Z is off track.

It's times like this where we need the intuitive leap. We've taken enough right foot, left foot steps before we got off track to be able to go back take those few steps to attempt a semi informed leap. We note an odd correlation with EBV, though we know not the relationship. We know there are geographic pockets, and the HERV theory fits what we know thus far. It's time to see if we can jump forward recognizing where we end up may be no closer to our desired endpoint of Z. Even if we don't end up at Z, maybe we will end up somewhere with a different starting point. Maybe this starting point will lead us down a heretofore unimagined path to Z, even if the Z we find is a solution to a completely different problem than the one for which we started looking.

Thanks so much for relaying your research. It is so heartening to hear of doctors seeking a cause. I too tested positive for EBV however never had mono. Interesting I had chicken pox (varicella zoster virus) in my 40s.....shortly later I was diagnosed with MS. A few years ago you wrote about Dr. Wheldon's antibacterial treatment. Is this the same notion?

No, not really the same notion. Dr. Weldon's antibiotic treatment is aimed at killing chlamydia pneumonia, a common bacterial infection which some claim to be the cause of MS. Who knows, maybe chlamydia pneumonia does trigger endogenous retroviruses, but that's not at the crux of the antibiotic protocol. There are lots still to be learned…

Thanks for this Marc: MS researchers in France published in 2008 the ideas that remnant bits of old retroviruses were re-activated from their dormant stage, hidden within DNA. The questions were at the time: "Why are they awakened today? - What do we do once the process is triggered? - can it be reversed?". I haven't heard of a sequel, but will look into this again

Good info Marc. Thanks for putting it together. I believe researchers will find the culprit and the cure, perhaps relatively soon. Of course I need nerve repair. Its a somewhat different solution from stopping MS. But I too am skeptical that the system as it exists now, a system that only looks to be getting worse, not better, will handle a cure like we all would like. Speaking of cures, heard of one lately? For anything?

Thank you for your very well researched article and the video of my talk. There is an up-dated talk I gave this year, which is on U-tube. I will be pleased to keep you informed on the research. This week we enrolled the first person onto the study.

The London trial is not due to report results for about two years, and I'm not sure that interim results will be reported. I'm sure that if the results are dramatic, we will hear about it sooner rather than later… I'll certainly be keeping an eye/ear open for any news…

Wow, thank you Mark for your dedication to sharing. I believe that this may be it. When I first presented M.S. symptoms, (22 years ago) I had Shigles at the same time. I have always known that there was a relationship. I can almost venture to picture myself in the future saying that I used to have M.S. You are a gifted writer,Jen

I am on this trial and was googling information that I could send to family members. This was perfect because it's well written, factual and in layman's terms! You helped me understand it and I'm on it!!Fingers crossed it gets us some answers, will keep you posted.

Excellent writing and research, Marc. If a HERV is responsible, it stands to reason that HSCT or autologous stem cells will never wipe out the condition. HSCT may cause an improvement for a time, but inevitably, MS is likely to show up again, down the road. The answer could involve umbilical cord blood stem cell (UBSC) l transplants or embryonic stem cell transplants (ESCT), screened for a gene mutation or an HERV. Both UBSC and ESCT do not have immunity built up and therefore no rejection risk. Interesting stuff!

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Regretfully, due to the high volume of e-mail received and the realities of living with progressive MS, I'll no longer be able to respond to all e-mails sent. I do read each note, and will do my best to answer as many messages as I can.

About Me

I'm Marc, a 53-year-old male, living in New York City with my lovely and wonderful wife Karen. Diagnosed with Primary Progressive Multiple Sclerosis in March of 2003, I now require a wheelchair to get around the city. I like to drive the wheelchair at full speed, thus the moniker "Wheelchair Kamikaze". I've managed to rig a camera to my chair, so I'm able to take videos and still photos from the unique vantage point of a wheelchair, which I intend to post here.
Before getting sick, I was the Director of DVD Production for one of the major international music companies. Yes, I was once a member of the Evil Empire...
Prior to my enlistment in the Evil Empire, I worked as a video producer and editor.
I grew up in New York City, and spent the 1980s in Boston (college and postcollege rock 'n roll craziness). During the 1990s, I lived in South Florida, until I woke up one morning and realized I was living in South Florida, came to my senses, and moved back to New York.
I hope you like my blog...